How to titrate the dose of acitrom (acenocoumarol) based on International Normalized Ratio (INR) levels?

Acitrom (Acenocoumarol) Dose Titration Based on INR

Titrate acenocoumarol to maintain INR between 2.0-3.0 (target 2.5) for most indications, adjusting doses based on INR measurements performed initially every 1-2 days until stable, then at intervals that maintain time in therapeutic range (TTR) ≥65%. 1

Target INR Range

• The therapeutic INR range is 2.0-3.0 for most indications including atrial fibrillation, venous thromboembolism, and mechanical heart valves 1
• Target an INR of 2.5 to maximize time spent within the therapeutic range 1
• The measurement error should not exceed ±0.5 from the target value of 2.5 (representing ±20% relative error) 1

Initial Dosing Phase

• Start with 5-10 mg daily for the first 2 days, then adjust based on INR response 1
• Measure INR every 1-2 days initially until the therapeutic range is achieved 1
• The goal is to achieve therapeutic INR within 7 days of treatment initiation 2

Dose Adjustment Strategy

When adjusting doses:

• If INR < 2.0: Increase weekly dose by 5-20% depending on how far below target
• If INR 2.0-3.0: Continue current dose
• If INR > 3.0 but < 5.0: Reduce weekly dose by 5-20%
• If INR ≥ 5.0: Hold dose temporarily, monitor closely for bleeding, and restart at lower dose when INR returns to therapeutic range 3

Monitoring Frequency

After achieving stable anticoagulation:

• Measure INR at intervals that maintain individual TTR ≥65% 1
• Most stable patients require monitoring every 2-4 weeks
• More frequent monitoring is needed after any dose adjustment (within 6-10 hours for heparin overlap, or 3-7 days for oral anticoagulant changes) 1

Critical Considerations for Acenocoumarol

Acenocoumarol has higher biological variability than longer-acting vitamin K antagonists like phenprocoumon or warfarin, requiring more vigilant monitoring 1

Key factors that predict over-anticoagulation and require closer monitoring: 3

• Artificial heart valve patients
• Poor medication compliance
• Addition of interacting medications
• Recent illness within the last month
• Higher body mass index and elevated C-reactive protein levels 4

Quality Metrics

• Aim for TTR ≥65% as the primary quality measure of anticoagulation control 1
• TTR below 65% is associated with significantly increased risk of stroke/systemic embolism (HR 2.55), mortality (HR 2.39), and major bleeding (HR 1.54) 1
• Calculate TTR using the Rosendaal method of linear interpolation between consecutive INR values 1

Common Pitfalls

• Do not use INR values >42 days apart for TTR calculations due to large uncertainties in fluctuation 1
• Random "one-off" INR values provide little insight into anticoagulation control quality 1
• Many bleeding events occur even within the therapeutic INR range of 2.0-3.0, emphasizing the importance of overall TTR rather than isolated measurements 1
• Patients with INR >5 have significantly more bleeding complications (21.8% vs 4.08%), though most are minor 3
• Concomitant aspirin use in patients with high INR variability requires especially close monitoring 5

Special Populations

In patients with unstable anticoagulation on acenocoumarol (≥50% of INR values out of range over 3 months), consider switching to warfarin, which may improve TTR from approximately 40% to 60% 4